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Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron
Author(s) -
MartínRuíz Marta,
Uranga José A.,
Mosinska Paula,
Fichna Jakub,
Nurgali Kulmira,
MartínFontelles Mª Isabel,
Abalo Raquel
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13499
Subject(s) - granisetron , cisplatin , medicine , nausea , vomiting , anesthesia , gastroenterology , visceral pain , chemotherapy , antiemetic , nociception , receptor
Background Cisplatin is a highly emetogenic antineoplastic drug and induces peripheral neuropathy when given in cycles. Granisetron, a 5‐HT 3 antagonist, is clinically used to prevent chemotherapy‐induced nausea/emesis and abdominal pain in irritable bowel syndrome. The effects of cisplatin on visceral sensitivity and those of granisetron in the context of cancer chemotherapy are not well known. Methods Adult male Wistar rats received two intraperitoneal injections 30 minutes apart: granisetron (1 mg kg −1 )/vehicle and cisplatin (6 mg kg −1 )/vehicle. Thereafter, nausea‐like behavior was measured as bedding intake for 4 hours, and gastric dysmotility was measured radiographically for 8 hours. Gastric weight and size were determined ex vivo and samples of the forestomach, corpus, ileum, and colon were obtained for histological analysis at 4 and 30 hours after cisplatin/vehicle. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation 2 hours after cisplatin/vehicle. Key Results Cisplatin‐induced bedding intake and gastric dysmotility, and granisetron blocked these effects, which occurred in the absence of frank mucositis. Visceral sensitivity was reduced to a similar extent by both drugs alone or in combination. Conclusions and Inferences Cisplatin‐induced bedding intake and gastric dysmotility were blocked by granisetron, confirming the involvement of serotonin acting on 5‐HT 3 receptors. Unexpectedly, visceral sensitivity to colonic distension was reduced, to the same extent, by cisplatin, granisetron, and their combination, suggesting important mechanistic differences with nausea and gastric dysmotility that warrant further investigation.